Making Connections Between Neural Structures in Culture

Even though it is now possible to fabricate organs and tissues in the laboratory, the vast majority of these structures can be made in isolation without compromising their functionality. Brain cells are quite different, since they required connections known as synapses with other brain cells. Synapses are also responsible for the functional interactions between different regions of the brain. Even though nerve cells (neurons) can be made in the laboratory, engineering connections between neurons is not trivial. Furthermore, some laboratories have used pluripotent stem cells to make portions of the brain in the laboratory, but getting those portions to properly connect with other regions of the brain has proven stultifying.

A new study by William Freed at the National Institutes of Health and his colleagues has designed a way to successfully grow multiple brain structures in the laboratory that form proper connections with each other in culture. This report is the first of its kind.

In particular, Freed and his co-workers defined a culture system for human pluripotent stem cells that produced connected human midbrain and neocortex.

The midbrain houses dopaminergic neurons (mDAs). These neurons use the neurotransmitter dopamine to signal to other neurons that reside elsewhere in the brain. Abnormalities of mDAs or connections between mDAs and other neurons are thought to play intimate roles in disorders like schizophrenia, Parkinson disease, attention-deficit disorder, Roulette’s syndrome, Lesch-Nyhan syndrome, and maybe even eating disorders.

Unfortunately, studying neocortical neurons and mDAs in isolation reveal little about the connections between them or their interactions. However, this new data from Freed that shows that it is possible to grow and interconnect these two types of neurons in culture provides neuroscientists with a powerful model system for examining this system and the abnormalities that afflict it.

The encourage connections between the two neuronal populations, mDAs and neocortical neurons were grown in special containers called “ibidi wound healing” dishes. Ibidi wound healing dishes contain two chambers separated by a removable barrier. Neocortical neurons were grown on one side and mDAs were grown on the other side. Both neuron populations were derived from human pluripotent stem cells. Once the cell cultures had properly formed, the barrier was removed and the two cell populations formed synapses across the barrier.

Freed is eager to examine human pluripotent stem cells derived from patients with neurological disorders that have been traced to abnormalities with connections between mDAs and other neuronal populations to study if neurons made from these patient’s cells properly synapse.

Clearly, this model system has great potential. This work was published in Restorative Neurology and Neuroscience, 2015 DOI: 10.3233/RNN-1140488.

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Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).